capmatinib dihydrochloride hydrate  (MedChemExpress)

Journal: The American Journal of Pathology

Article Title: Hepatocyte-Specific MET Deletion Exacerbates Acetaminophen-Induced Hepatotoxicity in Mice

doi: 10.1016/j.ajpath.2025.09.010

Figure Lengend Snippet: Hepatocyte growth factor (HGF)/MET signaling activation in human acute liver failure (ALF). A: Predicted alterations in canonical signaling pathways in human hepatocytes from acetaminophen (APAP)-induced ALF versus healthy livers identified by Ingenuity Pathways Analysis of publicly available single-nuclei RNA-sequencing data set (positive z score indicates predicted activation of a pathway). B: The dot plot illustrates average expression along with percentage of cells showing significant expression of cell proliferation genes in APAP-induced ALF livers versus healthy controls, based on analysis of publicly available spatial transcriptomics data set. C: Downstream gene network of HGF predicted to be activated in hepatocytes of APAP-induced ALF livers based on single-nuclei RNA-sequencing data analysis. D: Pie-chart illustrating that a large proportion (approximately 35%) of genes altered in human ALF were regulated by MET in the mouse APAP-induced liver injury (AILI) model [ie, differentially expressed genes (DEGs) in MET knockout (KO) vs wild-type (WT) mice]. E: Enrichment analysis using DAVID analysis software showing altered biological processes (Gene Ontology terms) in the MET-regulated genes from the mouse AILI model linked to human ALF (ie, 781 genes shown in orange color in D ). The number of genes associated with each pathway is indicated on the right side of the corresponding bar. F: Heat map depicting comparison analysis of altered canonical pathway in human ALF (vs HEA) and MET KO (vs WT) mice. G: Effect of MET inhibition on APAP-treated primary human hepatocytes. Representative images of propidium iodide (PI)-stained primary human hepatocytes, illustrating the percentage of cell death after 24 hours of treatment with 10 mM APAP alone or in combination with capmatinib (CAP) (MET inhibitor: 0.1 and 1 μM). ∗∗ P < 0.01 and ∗∗∗ P < 0.001 versus APAP 10 mM. Scale bar: 300 μm ( G ). ERAD, endoplasmic reticulum–associated protein degradation; HEA, healthy human liver tissue; TGF-β, transforming growth factor-β.

Article Snippet: Next day, the hepatocytes were washed with sterile phosphate-buffered saline and treated for 24 hours with 10 mM APAP alone or in combination with 0.1 or 1 μM capmatinib dihydrochloride hydrate (a MET inhibitor) (#HY-13404C; MedChemExpress) in fetal bovine serum–free media in the presence of HGF (50 ng/mL).

Techniques: Activation Assay, Protein-Protein interactions, RNA Sequencing, Expressing, Spatial Transcriptomics, Knock-Out, Software, Comparison, Inhibition, Staining

Journal: bioRxiv

Article Title: Oncogenic mutations convert MET from a pro-apoptotic tumor suppressor to an oncogenic driver

doi: 10.1101/2025.11.10.687614

Figure Lengend Snippet: (A) Immunoblot analysis of MET-induced downstream signaling pathways in edited 16HBE cells treated with 30 ng/mL HGF for 30 min, with or without capmatinib pre-treatment. Cells were pre-treated with 1 µM capmatinib for 90 minutes prior to HGF stimulation. Immunoblots are representative of three independent biological experiments. (B-C) Quantification of relative wound density in migration assays (8 h post-HGF stimulation) and invasion assays (in Matrigel, 3 days post-HGF stimulation) following stimulation with 30 ng/mL HGF, with or without 1 µM capmatinib pre-treatment for 90 minutes. Values represent means ± SD from three independent experiments. Statistical significance was determined by two-way ANOVA followed by appropriate post hoc tests. ns (not significant), * (p < 0.05), ** (p < 0.01), *** (p < 0.001), **** (p < 0.0001). (D) Membrane permeability was measured five days after serum starvation with or without 1 µM capmatinib. The fluorescence signal was normalized to cell confluence. n=5; mean ± SD; representative of two independent experiments. Statistical significance was determined by one-way ANOVA. ns (not significant). (E-G) Tumor growth in and survival of NSG-huHGF mice injected subcutaneously with genome-edited cells. Daily treatment with vehicle or capmatinib (10 mg/kg/day) was initiated when at least one tumor per mouse reached approximately 100 mm³. (E) Tumor growth curves from the start of treatment. Data represent mean tumor volumes ± SEM. (F) Tumor volume at day 21; each point represents an individual tumor. (G) Kaplan–Meier curve showing overall survival. Statistical significance was assessed with unpaired two-tailed t -tests for tumor volume comparisons (E, F) and the log-rank (Mantel–Cox) test for survival (G). The hazard ratio (HR) is indicated. ns (not significant), * (p < 0.05).

Article Snippet: Capmatinib (#HY-13404 MedChemExpress) was freshly resuspended in vehicle (1% methylcellulose, 0.5% Tween-80 in water) at 2 mg/mL.

Techniques: Western Blot, Protein-Protein interactions, Migration, Membrane, Permeability, Fluorescence, Injection, Two Tailed Test

Journal: bioRxiv

Article Title: Oncogenic mutations convert MET from a pro-apoptotic tumor suppressor to an oncogenic driver

doi: 10.1101/2025.11.10.687614

Figure Lengend Snippet: (A) Immunoblot analysis of MET-induced downstream signalling pathways in A549 editing cells treated with 30 ng/mL HGF for 30 minutes, with or without capmatinib pre-treatment. Cells were pre-treated with 1 µM capmatinib for 90 minutes prior to HGF stimulation. Immunoblots are representative of three independent biological experiments. (B) Membrane permeability was measured five days after serum starvation with or without 1 µM of capmatinib. Fluorescence signal was normalized to cell confluence. Data represent means ± SD from two independent biological experiments, each including at least six technical replicates. Statistical significance was determined by one-way ANOVA. **** ( p < 0.0001).

Article Snippet: Capmatinib (#HY-13404 MedChemExpress) was freshly resuspended in vehicle (1% methylcellulose, 0.5% Tween-80 in water) at 2 mg/mL.

Techniques: Western Blot, Membrane, Permeability, Fluorescence

Journal: bioRxiv

Article Title: Oncogenic mutations convert MET from a pro-apoptotic tumor suppressor to an oncogenic driver

doi: 10.1101/2025.11.10.687614

Figure Lengend Snippet: (A) Tumor growth of SCID mice injected subcutaneously with Hs746T cells. Daily treatment with vehicle or capmatinib (2.5 mg/kg/day) was initiated fifteen days after cells injection. Data represent mean tumor volume ± SEM. (B) Immunoblot analysis of MET-induced downstream signalling pathways in Hs746T treated with or without capmatinib 1 µM for 2 h. Immunoblots are representative of two independent biological experiments.

Article Snippet: Capmatinib (#HY-13404 MedChemExpress) was freshly resuspended in vehicle (1% methylcellulose, 0.5% Tween-80 in water) at 2 mg/mL.

Techniques: Injection, Western Blot